RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis.

Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that induces diarrhea and death in neonatal piglets, resulting in substantial economic losses to the global swine industry. The mechanisms of PEDV infection and the roles of host factors are still under exploration. In this study, we used the ferroptosis pathway downstream target activator (1S,3R)-RSL3 compound as a starting point, combined with the interactions of N-acetylcysteine and deferoxamine, to elucidate the effects of a series of compounds on PEDV proliferation. We also established glutathione peroxidase 4 (GPX4) gene overexpression to further elucidate the relationship between the ferroptosis pathway and PEDV. (1S,3R)-RSL3 inhibited PEDV replication in Vero cells, while N-acetylcysteine and deferoxamine promoted its proliferation. In addition, (1S,3R)-RSL3 mainly affected the replication stage of PEDV. Overexpression of GPX4 promoted PEDV proliferation, indicating that the ferroptosis pathway could influence PEDV replication in Vero cells. This study focused on the mechanism of (1S,3R)-RSL3 inhibition on PEDV, laying the foundation for exploring the pathogenic mechanisms of PEDV and drug development.

E. coli diversity: low in colorectal cancer.

BACKGROUND: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. METHODS: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. RESULTS: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. CONCLUSIONS: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.

Repeated CyberKnife stereotactic body radiation therapy in hepatocellular carcinoma.

BACKGROUND: To explore the survival and side effects of repeated CyberKnife stereotactic body radiation therapy (CK-SBRT) on hepatocellular carcinoma patients. METHODS: 24 HCC patients were collected at The Fifth Medical Center of PLA General Hospital from November 2011 to July 2016. They received second-course CK-SBRT with a prescribed dose of 50(48-55) Gy/5-8fx, and a single dose of 10 (7-11) Gy/fx. Cumulative overall survival rates (OS), progression-free survival rates (PFS) and local control rates (LC) were calculated by Kaplan-Meier method. RESULTS: All patients finished their radiotherapy plans. The 1-,2- and 3-year cumulative OS rate were 95.8,81.1 and 60.8%. The 1-,2- and 3-year LC rate were 95.5,90.7 and 90.7%, respectively. The 1-, 2- and 3-year PFS were 74.8, 49.2 and 39.4%, respectively. 16 patients complained of fatigue during second-course therapy, 2 patients showed Grade 2 gastrointestinal reaction, 1 patient was diagnosed radiation-induced liver disease and none died. PFS was significantly higher in the interval time < 12 months group than in the interval time ≥ 12 months group (p = 0.030). CONCLUSIONS: It is preliminarily believed that re-CK-SBRT is an effective and safe treatment for HCC patients, but the treatment criteria should be strictly controlled.

Polyphyllin G exhibits antimicrobial activity and exerts anticancer effects on human oral cancer OECM-1 cells by triggering G2/M cell cycle arrest by inactivating cdc25C-cdc2.

Plant natural products have long been considered to be important sources of bioactive molecules. A large number of antimicrobial and anticancer agents have been isolated form plants. In the present study we evaluated the antimicrobial and anticancer activity of a plant derived secondery metabolite, Polyphyllin G. The results of antibacterial assays showed that Polyphyllin G prevented the growth of both Gram-positive and Gram-negative bacteria with minimum inhibitory concentrations (MICs) ranging from 13.1 to 78 µg/ml. Antifungal activity measured as inhibition of mycelium growth ranged between 38.32 and 56.50%. Further Polyphyllin G was also evaluated against a panel of cancer cell lines. The IC50 of Polyphyllin G ranged from 10 to 65 µM. However the IC50 of Polyphyllin G was found to be comparatively high (120 µM) against the normal FR2 cancer cell line. The lowest IC50 of 10 µM was found against the oral cancer cell line OECM-1. Therefore further studies were carried out on this cell line only. Our results indicated that Polyphyllin G induced cell arrest in oral cancer OECM-1 cells by inactivation of cdc25C-cdc22 via ATM-Chk 1/2 stimulation. Therefore, we propose that Polyphyllin G might prove a lead molecule in the management of oral cancers and at the same time may prevent the growth of opportunistic microbes.